Diazo reagents with small steric footprints for simultaneous arming/SAR studies of alcohol-containing natural products via O-H insertion

Supakarn Chamni, Qing Li He, Yongjun Dang, Shridhar Bhat, Jun O. Liu, Daniel Romo

Research output: Contribution to journalArticle

Abstract

Natural products are essential tools for basic cellular studies leading to the identification of medically relevant protein targets and the discovery of potential therapeutic leads. The development of methods that enable mild and selective derivatization of natural products continues to be of significant interest for mining their information-rich content. Herein, we describe novel diazo reagents for simultaneous arming and structure-activity relationship (SAR) studies of alcohol-containing natural products with a small steric footprint, namely, an α-trifluoroethyl (HTFB) substituted reagent. The Rh(II)-catalyzed O-H insertion reaction of several natural products, including the potent translation inhibitor lactimidomycin, was investigated, and useful reactivity and both chemo- and site (chemosite) selectivities were observed. Differential binding to the known protein targets of both FK506 and fumagillol was demonstrated, validating the advantage of the smaller steric footprint of α-trifluoroethyl derivatives. A p-azidophenyl diazo reagent is also described that will prove useful for photoaffinity labeling of low affinity small molecule protein receptors.

Original languageEnglish (US)
Pages (from-to)1175-1181
Number of pages7
JournalACS chemical biology
Volume6
Issue number11
DOIs
StatePublished - Nov 18 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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